Synthesis and characterization of gelatin/lignin hydrogels as quick release drug carriers for Ribavirin.

In this study, hydrogels based on gelatin and lignin were fabricated as efficient drug carriers for Ribavirin. The obtained hydrogels were characterized by scanning electron microscopy (SEM), ATR-FTIR spectroscopy, differential scanning calorimetry (DSC), mechanical compression and rheometry. Results showed that the pore structure, viscoelastic behavior and swelling ability significantly influenced by varying lignin content and crosslinker ratio. By increasing the crosslinker N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) content, the pore size became smaller, while increasing the lignin content resulted in larger pores. In addition, all hydrogels show strong shear thinning behavior. Ribavirin was used as a drug model, and its release rate was enhanced by increasing lignin content in the binary hydrogel structure. A higher Ribavirin cumulative release was observed for gelatin/lignin with higher lignin content (3 %) hydrogel. These findings emphasize the chemical composition on the structure and the release behavior of lignin-containing hydrogels.

Biocompatibility evaluation for the developed hydrogel wound dressing - ISO-10993-11 standards -in vitroandin vivostudy.

Assessment of biocompatibility for the developed wound dressing plays a significant role in translational studies. In the present research work, a wound dressing has been developed using gelatin, hyaluronic acid and chondroitin sulfate using EDC as crosslinker in a specific manner. The characterized hydrogel wound dressing was evaluated for its biocompatibility studies by means of ISO-10993-11 medical device rules and standards. Various parameters like skin sensitization test, acute systemic toxic test, implantation study, intracutaneous reactivity test,in vitrocytotoxicity test and bacterial reverse mutation test, were evaluated and the results demonstrated its safety for the pre-clinical investigation.

Preclinical efficacy study of a porous biopolymeric scaffold based on gelatin-hyaluronic acid-chondroitin sulfate in a porcine burn injury model: role of critical molecular markers (VEGFA, N-cadherin, COX-2), gamma sterilization efficacy and a comparison of healing potential to Integra™.

Development of scaffold from biopolymers can ease the requirements for donor skin autograft and plays an effective role in the treatment of burn wounds. In the current study, a porous foam based, bilayered hydrogel scaffold was developed using gelatin, hyaluronic acid and chondroitin sulfate (G-HA-CS). The fabricated scaffold was characterized physicochemically for pre- and post-sterilization efficacy by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA).In-vitrostudies proved that the scaffold promoted cellular proliferation. The efficacy of G-HA-CS scaffold was compared with Integra™ at different time points (7, 14, 21 and 42 days), in a swine second degree burn wound model. Remarkable healing potential of the scaffold was evident from the wound contraction rate, reduction of IL-6, TNF-αand C3. The expression of healing markers TGF-ß1 and collagen 1 revealed significant skin regeneration with regulated fibroblast activation towards the late phase of healing (p< 0.001 at day 21 and 42 vs. control). Expression of Vascular Endothelial Growth Factor A (VEGFA), vimentin and N-cadherin were found to favor angiogenesis and skin regeneration. Mechanistically, scaffold promoted wound healing by modulation of CD-45, cyclooxygenase-2 and MMP-2. Thus, the promising results with foam based scaffold, comparable to Integra™ in swine burn injury model offer an innovative lead for clinical translation for effective management of burn wound.

Nanofibrous artificial skin substitute composed of mPEG-PCL grafted gelatin/hyaluronan/chondroitin sulfate/sericin for 2nd degree burn care: in vitro and in vivo study.

The aim of this study was to investigate the efficacy of a skin substitute composed of mPEG-PCL-grafted-gelatin (Bio-Syn)/hyaluronan/chondroitin sulfate/sericin and to study its in vitro biocompatibility with human fibroblasts, human keratinocytes and hMSCs in terms of cellular adhesion and proliferation (∼5-6 fold). mPEG-PCL was grafted into a gelatin backbone via a Michael addition reaction to prepare Bio-Syn and it was characterized using ATR-FTIR, 1H NMR and TNBS assay. Additionally, keratinocyte-hMSC contact co-culture studies showed that Bio-Syn composite scaffolds loaded with sericin promote hMSCs' epithelial differentiation with regard to qRT-PCR gene expression (ΔNp63α and keratin 14) and expression of various epithelial markers (Pan-cytokeratin, ΔNp63α and keratin 14). In vivo efficacy studies on a 2nd degree burn wound model in Wistar rats showed an improved rate of wound contraction, histology (H&E and Van Gieson's staining) and pro-healing marker (hexosamine, hydroxyproline, etc.) expression in granular tissue compared to using the commercial dressing Neuskin™ and a cotton gauze control.